Proteolysis of von Willebrand factor (vWF) normally occurs through the action of a plasma enzyme that has recently been characterized; it accounts for the small quantities of cleavage products normally present in the circulation, and its inhibition can lead to the disease called thrombotic thrombocytopenic purpura (TTP). We have developed a better and more rapid assay to evaluate the cleavage of vWF and have characterized patients with a TTP-like syndrome to detect those with low vWF cleaving protease activity. The assay does not require specialized reagents and can be completed within 6-8 hours on patient plasma. We are working on a purification process to isolate plasma vWF protease and better characterize its function.